Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using H-1 and C-13 NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 mu g/ml. The cytotoxic activity of compound 5c and 5f against BALE/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 mu g/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopol and hTopoll and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine. (c) 2016 Elsevier B.V. All rights reserved.